Genetic Architecture of the APM1 Gene and Its Influence on Adiponectin Plasma Levels and Parameters of the Metabolic Syndrome in 1,727 Healthy Caucasians

Genetic Architecture of the APM1 Gene and Its Influence on Adiponectin Plasma Levels and Parameters of the Metabolic Syndrome in 1,727 Healthy Caucasians Iris M. Heid 1 2 , Stefanie A. Wagner 1 3 , Henning Gohlke 1 , Bernhard Iglseder 4 , Jakob C. Mueller 5 , Paula Cip 3 , Günther Ladurner 4 , Raphael Reiter 3 , Andreas Stadlmayr 3 , Vitolds Mackevics 3 , Thomas Illig 1 , Florian Kronenberg 6 and Bernhard Paulweber 3 1 GSF-National Research Center for Environment and Health, Institute of Epidemiology, Neuherberg, Germany 2 Department of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany 3 First Department of Internal Medicine, St. Johann Spital, Paracelsus Private Medical University Salzburg, Salzburg, Austria 4 Department of Neurology, Paracelsus Private Medical University Salzburg, Salzburg, Austria 5 Institute for Medical Statistics and Epidemiology & Institute for Psychiatry and Psychotherapy, Clinic “Rechts der Isar,“ Technical University, Munich, Germany 6 Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria Address correspondence and reprint requests to Florian Kronenberg MD, Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schöpfstr. 41, A-6020 Innsbruck, Austria. E-mail: florian.kronenberg{at}i-med.ac.at Abstract The associations of the adiponectin ( APM1 ) gene with parameters of the metabolic syndrome are inconsistent. We performed a systematic investigation based on fine-mapped single nucleotide polymorphisms (SNPs) highlighting the genetic architecture and their role in modulating adiponectin plasma concentrations in a particularly healthy population of 1,727 Caucasians avoiding secondary effects from disease processes. Genotyping 53 SNPs (average spacing of 0.7 kb) in the APM1 gene region in 81 Caucasians revealed a two-block linkage disequilibrium (LD) structure and enabled comprehensive tag SNP selection. We found particularly strong associations with adiponectin concentrations for 11 of the 15 tag SNPs in the 1,727 subjects (five P values